Table 1.

SARS-CoV-2 CD4⁺ and CD8⁺ T cell responses in infection and vaccination.

		CD4+ T cell responses	Ref.	CD8+ T cell responses	Ref.
Infection	Adults	−100% recovered patients have activated cells—Produce IFNγ, TNFα, IL2 - Express CD134, CD137 - Recruited early during acute infection - HLA-DPB1*04/S166−180 is a dominant SARS-CoV-2-specific epitope following infection	(18, 21, 22, 28, 29)	−70% recovered patients activated cells - Produce IFNγ, TNFα, IL2, GzB - Express CD69, CD137 - Recruited later during infection at convalescence - HLA-B*07:02/N105−113 is a dominant SARS-CoV-2-specific epitope following infection (38 × larger than B7/N257, A2/S269 and A24/S1208)	(18, 21, 22, 26, 29–32)
	Children	- Reduced response magnitude compared with adults - T naïve in children > T naïve in adults	(22)	- Reduced response magnitude compared with adults	(22)
	Severe	- Reduced structural response - Hyperactivated CD25+ CD4+ T cells expressing furin - Increased TFH2, reduced TFH1 and TFH17	(33, 34)	- Reduced response - Less exhaustion, defined by coexpression of PD-1, CD38 and HLA-DR than mild patients.	(33, 35)
Vaccination		- Induction of strong CD4+ responses across most vaccine platforms - No significant differences found in studies comparing two vaccines in parallel	(36–40)	- Induction of CD8+ responses across most vaccine platforms (at lower levels than CD4+ T cell fold changes)	(36–40)
Hybrid immunity		- Increased responses compared with infection induced immunity alone. - One dose of mRNA vaccination boosts previous response from natural infection or ChAdOx1 nCov-19 vaccination - Two doses did not boost responses further	(41, 42)	- mRNA vaccination boosts previous response after one dose - Further boosting is seen after two doses alongside increased memory responses	(42)
Crossreactivity Infection		- Unexposed healthy individuals have crossreactive CD4+ T cells against ORF1a/b nsp7 and nsp13 proteins - Dominant epitopes DPB1*04/S166 and /S186 are conserved in currently known VoCs	(20, 28, 43, 44)	- Dominant epitope B7/N105 epitope is conserved in currently known VoCs	(21, 26, 32, 45)
	Vaccination	- mRNA vaccination induces CD4+ T cells crossreactive to several VoCs - Back boosting of HLA-DPB1*04/S816−830 responses by mRNA vaccination. Found in 20% unexposed positive, 50% patients and 97% vaccinees. - 7% of epitopes affected in VoC, crossreactivity maintained	(36, 39, 46, 47)	- mRNA vaccine recipients maintain crossreactive CD8+ - 3% of epitopes affected in VoC, crossreactivity maintained	(36, 39)